Development and Characterization of Pullulan-Based Orodispersible Films of Iron.

Iron deficiency is the principal cause of nutritional anemia and it constitutes a major health problem, especially during pregnancy. Despite the availability of various non-invasive traditional oral dosage forms such as tablets, capsules, and liquid preparations of iron, they are hard to consume for special populations such as pregnant women, pediatric, and geriatric patients with dysphagia and vomiting tendency. The objective of the present study was to develop and characterize pullulan-based iron-loaded orodispersible films (i-ODFs). Microparticles of iron were formulated by a microencapsulation technique, to mask the bitter taste of iron, and ODFs were fabricated by a modified solvent casting method. Morphological characteristics of the microparticles were identified by optical microscopy and the percentage of iron loading was evaluated by inductively coupled plasma optical emission spectroscopy (ICP-OES). The fabricated i-ODFs were evaluated for their morphology by scanning electron microscopy. Other parameters including thickness, folding endurance, tensile strength, weight variation, disintegration time, percentage moisture loss, surface pH, and in vivo animal safety were evaluated. Lastly, stability studies were carried out at a temperature of 25 °C/60% RH. The results of the study confirmed that pullulan-based i-ODFs had good physicochemical properties, excellent disintegration time, and optimal stability at specified storage conditions. Most importantly, the i-ODFs were free from irritation when administered to the tongue as confirmed by the hamster cheek pouch model and surface pH determination. Collectively, the present study suggests that the film-forming agent, pullulan, could be successfully employed on a lab scale to formulate orodispersible films of iron. In addition, i-ODFs can be processed easily on a large scale for commercial use.

Development and Characterization of PEGDA Microneedles for Localized Drug Delivery of Gemcitabine to Treat Inflammatory Breast Cancer.

Inflammatory breast cancer (IBC) is one of the most belligerent types of breast cancer. While various modalities exist in managing/treating IBC, drug delivery using microneedles (MNs) is considered to be the most innovative method of localized delivery of anti-cancer agents. Localized drug delivery helps to treat IBC could limit their adverse reactions. MNs are nothing but small needle like structures that cause little or no pain at the site of administration for drug delivery via layers of the skin. The polyethylene glycol diacrylate (PEGDA) based MNs were fabricated by using three dimensional (3D) technology called Projection Micro-Stereo Lithography (PµSL). The fabricated microneedle patches (MNPs) were characterized and coated with a coating formulation comprising of gemcitabine and sodium carboxymethyl cellulose by a novel and inventive screen plate method. The drug coated MNPs were characterized by various instrumental methods of analysis and release profile studies were carried out using Franz diffusion cell. Coat-and-poke strategy was employed in administering the drug coated MNPs. Overall, the methods employed in the present study not only help in obtaining MNPs with accurate dimensions but also help in obtaining uniformly drug coated MNPs of gemcitabine for treatment of IBC. Most importantly, 100% drug release was achieved within the first one hour only.

A Comprehensive Review of Patented Technologies to Fabricate Orodispersible Films: Proof of Patent Analysis (2000-2020).

Orodispersible films (ODFs)are ultra-thin, stamp-sized, rapidly disintegrating, and attractive oral drug delivery dosage forms best suited for the pediatric and geriatric patient populations. They can be fabricated by different techniques, but the most popular, simple, and industrially applicable technique is the solvent casting method (SCM). In addition, they can also be fabricated by extrusion, printing, electrospinning, and by a combination of these technologies (e.g., SCM + printing). The present review is aimed to provide a comprehensive overview of patented technologies of the last two decades to fabricate ODFs. Through this review, we present evidence to adamantly confirm that SCM is the most popular method while electrospinning is the most recent and upcoming method to fabricate ODFs. We also speculate around the more patent-protected technologies especially in the domain of printing (two or three-dimensional), extrusion (ram or hot-melt extrusion), and electrospinning, or a combination of the methods thereof.

Orodispersible films: Conception to quality by design.

Orodispersible films (ODFs) are ultra-thin, stamp-sized, elegant, portable and patient-centric pharmaceutical dosage forms that do not need water to be ingested. They are particularly useful for paediatric and geriatric patient populations with special needs such as dysphagia, Parkinson's disease, and oral cancer. Accordingly, they hold tremendous potential in gaining patient compliance, convenience and pharmacotherapy. In the present review, conception and evolution of ODFs as a product and its technology are discussed. The review continues by providing overview about the potential of ODFs as carriers for delivering drugs, herbal extracts, probiotics and vaccines. Besides, strategies employed in drug cargo loading, taste masking of bitter drugs and enhancing drug stability are discussed. Finally, the review concludes by providing a brief overview about quality by design (QbD) principles in development of ODFs.

Prospection of chitosan and its derivatives in wound healing: Proof of patent analysis (2010-2020).

Disruption in the normal anatomy and physiology of the skin often leads to wound formation. Its healing is a pretty complex and dynamic biological process with different phases. While there are many biopolymers (and their derivatives) for wound healing purposes. One of the most popular, promising, progressive and attention-grabbing biopolymers is 'chitosan'. It is a polysaccharide biopolymer that has tremendous potential in augmenting the process of wound healing. Most importantly, the derivatives of chitosan have heavily attracted the scientific community's attention to employing them in various formulations for wound healing applications. The prime focus of the present review is to provide scientific and technological prospection about chitosan and its derivatives for wound healing activity, starting from 2010 to 2020. Besides, the review also focuses about toxicity, different formulations and products of chitosan that are currently under clinical trials for wound healing purposes are described. Through this review, we present evidence that abundantly confirms that there is a growing interest in the domain of wound healing using novel, inventive, useful and patent protected chitosan derivatives. We speculate the possibility of more patent protected chitosan derivatives in the future for wound healing applications.

Printing Methods in the Production of Orodispersible Films.

Orodispersible film (ODF) formulations are promising and progressive drug delivery systems that are widely accepted by subjects across all the age groups. They are traditionally fabricated using the most popular yet conventional method called solvent casting method. The most modern and evolving method is based on printing technologies and such printed products are generally termed as printed orodispersible films (POFs). This modern technology is well suited to fabricate ODFs across different settings (laboratory or industrial) in general and in a pharmacy setting in particular. The present review provides an overview of various printing methods employed in fabricating POFs. Particularly, it provides insight about preparing POFs using inkjet, flexographic, and three-dimensional printing (3DP) or additive manufacturing techniques like filament deposition modeling, hot-melt ram extrusion 3DP, and semisolid extrusion 3DP methods. Additionally, the review is focused on patenting trends in POFs using ESPACENET, a European Patent Office search database. Finally, the review captures future market potential of 3DP in general and ODFs market potential in particular.

The potential of ODFs as carriers for drugs/vaccines against COVID-19.

COVID-19 has spread out its wings across the globe and is taking away many lives. Millions of people are (self) quarantined to prevent the spread of this viral disease. World Health Organization (WHO) has affirmed that there is not any medicine for COVID-19. Besides, there is also no single drug that is approved by any regulatory agency for usage against this dangerous disease. Researchers across the globe are working tirelessly to fix an end to this virus and to save precious lives. While the research is in full swing, one is not sure whether they would come up with a chemical/herbal drug or a vaccine. Irrespective of the type of active ingredient for COVID-19, one needs to have a proper system to deliver the identified active ingredient to subjects/patients across the globe. Orodispersible films (ODFs) are excellent and attractive drug delivery carriers that have the potential to deliver drugs, herbal extracts, and vaccines. They are apt for patients who have a problem consuming traditional drug products such as tablets or capsules. The beauty of this dosage form is that it does not need water to consume by the subjects and can be readily administered to the tongue. The present review highlights the true potential of ODFs to act as a carrier for the delivery of various antiviral drugs/herbs/vaccines.

Microneedles Drug Delivery Systems for Treatment of Cancer: A Recent Update.

Microneedles (MNs) are tiny needle like structures used in drug delivery through layers of the skin. They are non-invasive and are associated with significantly less or no pain at the site of administration to the skin. MNs are excellent in delivering both small and large molecules to the subjects in need thereof. There exist several strategies for drug delivery using MNs, wherein each strategy has its pros and cons. Research in this domain lead to product development and commercialization for clinical use. Additionally, several MN-based products are undergoing clinical trials to evaluate its safety, efficacy, and tolerability. The present review begins by providing bird's-eye view about the general characteristics of MNs followed by providing recent updates in the treatment of cancer using MNs. Particularly, we provide an overview of various aspects namely: anti-cancerous MNs that work based on sensor technology, MNs for treatment of breast cancer, skin carcinoma, prostate cancer, and MNs fabricated by additive manufacturing or 3 dimensional printing for treatment of cancer. Further, the review also provides limitations, safety concerns, and latest updates about the clinical trials on MNs for the treatment of cancer. Furthermore, we also provide a regulatory overview from the "United States Food and Drug Administration" about MNs.

Characterization of Orodispersible Films: An Overview of Methods and Introduction to a New Disintegration Test Apparatus Using LDR - LED Sensors.

Orodispersible Film (ODF) is a promising and progressive dosage form that offers exceptional drug delivery benefits to patients. Indeed, they are the most transformational alternatives to traditional/conventional dosage forms such as tablets and capsules. ODFs are portable and highly comfortable for self-administration by patients with swallowing problems. The key to gain end-user acceptance is to have an ODF with outstanding quality. Poor quality may lead to choking or spitting, accordingly leading to a lack of compliance. It is vital to employ suitable experimental methodologies that facilitate characterization or determination of the quality of ODF. Nonetheless, there are no standard techniques prescribed in official compendia of any country. But, there is a consensus in the thin-film research community about the characterization techniques that one relies on deciding the quality of an ODF. We review various experimental techniques and highlight its importance in determining the performance and quality of an ODF. We provide a relatively novel and inventive disintegration test apparatus, which works using 'Light Dependent Resistor (LDR) and Light Emitting Diode (LED) sensors' for clear and accurate determination of start and end disintegration time of an ODF.